The initiation of interleukin-mediated events requires the activation of phospholipase A2 to produce arachidonic acid (AA) which is subsequently metabolized ed by the lipoxygenase pathway. This pathway seems to be required for IL 2-induced elevation of cyclic GMP, stimulation of IFN Gamma production and the regulation of cellular proliferation. Lipoxygenation of AA is also required for IL 1 to induce IL 2 release. Taken together, these data suggest that products of lipoxygenase metabolism modulate the effects of interleukins, whereas the products of cyclooxygenase pathway (produced predominantly by macrophages) may inhibit the activity of lymphokines as well as their production. Based on this proposed model of the intermediate metabolism required for lymphokine-mediated activities, it is now possible to conceive strategies for the identification of new pharmacological agents for the amplification and inhibition of immune responses. We have shown and increase in opiate receptors on activated T lymphocytes over the level of Beta-endorphin binding by resting lymphocytes. Associated with increased receptor appearance is the ability of Beta-endorphin to modulate (uncouple) T-lymphocyte responses to prostaglandins. The mechanism of Beta-endorphin activity is mediated through specific opiate receptors and does not directly involve IL 2 receptors or the growth promoting activity of IL 2. Both T-lymphocyte proliferation and NK activity are suppressed by the endogenous production of exogenous addition of PGE2. Based on our data, it is reasonable to assume that the enhancement of IL 2-mediated lymphocyte growth and function by Beta-endorphin may be attributed to the ability of Beta-endorphin to mitigate the inhibitory effects of PGE2 produced in PBL cultures.